ABSTRACT
@#[摘 要] 以靶向PD-1/PD-L1和CTLA-4为代表的免疫检查点阻断治疗在实体瘤的治疗中取得了不俗疗效，但仅有不到30%的患者能够从中受益的现实表明，还存在其他免疫检查点分子介导的免疫抑制。B7H3属于免疫球蛋白超家族B7家族成员，与CTLA-4/PD-1主要表达在T细胞并介导后者的免疫抑制或耗竭不同，B7H3蛋白不仅诱导性表达在免疫细胞，还组成性高表达在多种肿瘤细胞和肿瘤相关脉管系统。B7H3不仅能够激活多条信号通路直接促进肿瘤细胞恶性表型，还可以通过重塑肿瘤免疫抑制微环境间接促进肿瘤的进展、转移和耐药。因此，基于B7H3的多项靶向抗肿瘤策略，包括特异性抗体、抗体偶联药物及CAR-T细胞等均已进入临床试验并展示出较好的应用前景。但总体而言，该领域的研究依然处于探索阶段，在相互作用受体的鉴定、降低毒性、打破耐药及联合用药策略优化等方面还面临着许多问题和挑战亟待突破。
ABSTRACT
@# Immune-checkpoint blockade (ICB) therapy, especially PD-1/PD-L1 and CTLA-4 blocking antibodies, has achieved surprising curative effects in advanced cancer patients. The US FDAhas approved ICB treatment for melanoma, small cell lung carcinoma, kidney carcinoma, and all solid tumors with microsatellite instability. However, with the expansion and deepening of pre-clinical trials and clinical applications in recent years, the limitations of ICB immunotherapy have gradually emerged. For example, even in well-responded tumor types, the effective rate of ICB therapy is only 20%-30%, and there are even cases with tumor progression and metastasis. Therefore, what factors determine or limit the effectiveness of ICB therapy? What kind of patients can benefit from it? Which biomarkers can be used for screening beneficiary patients, evaluating therapeutic outcomes and prognosis? The clarification of above issues will greatly promote the research in this field. In this review, based on the anti-tumor mechanism of ICB, we discuss the recent progress in this field, with an emphasis on the key factors restricting the efficacy of ICB treatment and the current combined therapeutic strategies with ICB, aiming to reveal which biomarkers can be used in the concomitant diagnosis of ICB therapy and the future application perspective of ICB combined therapies, to provide reference for the precision medicine of ICB anti-tumor therapy.